Experimental therapy of prostate cancer with novel natural product anti‐cancer ginsenosides

<jats:title>Abstract</jats:title><jats:sec><jats:title>BACKGROUND</jats:title><jats:p>Ginseng and its components exert various biological effects, including antioxidant, anti‐carcinogenic, anti‐mutagenic, and anti‐tumor activity, and recent research has focused on their value in human cancer prevention and treatment. We recently isolated 25‐hydroxyprotopanaxadiol (25‐OH‐PPD) and 25‐hydroxyprotopanaxatriol (25‐OH‐PPT) from <jats:italic>Panax ginseng</jats:italic> and evaluated their anti‐cancer activity in vitro.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>We compared the effects of the two compounds on human prostate cancer LNCaP and PC3 cells in vitro and in a mouse PC3 xenograft tumor model. We also accomplished a preliminary determination of the mechanisms of action of the compounds.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>25‐OH‐PPD, but not 25‐OH‐PPT, inhibited prostate cancer cell growth and proliferation, induced apoptosis, and led to arrest in the G1 phase of the cell cycle. In nude mice bearing PC3 xenograft tumors, 25‐OH‐PPD inhibited tumor growth in a dose‐dependent manner and could be safely combined with chemotherapeutic agents (taxotere and gemcitabine) and radiation therapy to improve the anti‐tumor effects. Further, in both PC3 and LNCaP cell lines, 25‐OH‐PPD increased expression of p21, p27, and Bax, induced PARP cleavage and activated caspases. The compound also reduced expression of MDM2, E2F1, Bcl2, cdk2/4/6, and cyclin D1, which correlated with the cell cycle arrest in G1 and the decrease in proliferation. Moreover, 25‐OH‐PPD demonstrated low toxicity to non‐cancer cells and no observable host toxicity in animals either alone or in combination with conventional therapies.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS</jats:title><jats:p>The newly identified ginsenoside 25‐OH‐PPD may have potential as a novel prostate cancer therapeutic agent. Prostate 68:809–819, 2008. © 2008 Wiley‐Liss, Inc.</jats:p></jats:sec>